CYLD改变与人类乳头状瘤病毒阳性头颈癌的转移和预后不良有关

IF 2.3 3区医学 Q1 OTORHINOLARYNGOLOGY

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck Pub Date : 2024-09-30 DOI:10.1002/hed.27944

Zhibin Cui, Hyunseok Kang, Hua Li, Eliot D Lee, Yoon Se Lee, Christopher N Peterson, Steven R Long, Jennifer R Grandis, Daniel E Johnson

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引用次数: 0

摘要

背景：人乳头瘤病毒（HPV）相关头颈部鳞状细胞癌（HNSCC）是一种新出现的流行病，HPV阳性患者中有一部分会出现侵袭性疾病和转移。CYLD基因在HPV阳性HNSCC中经常发生改变，但这些改变在疾病进展中所起的作用却鲜为人知：方法：我们发现了 11 例具有 CYLD 基因改变的 HPV 阳性 HNSCC 患者，并评估了他们的临床病程。我们还鉴定了一种独特的、HPV 阳性、转移性 HNSCC 患者衍生异种移植物（PDX）：结果：与野生型CYLD的HPV阳性转移性患者相比，所有11名患者都发生了转移，总生存期缩短。转移性PDX携带CYLD突变（S371*），并表现出连接蛋白43（一种潜在的抗转移蛋白）表达减少。我们还研究了S371*突变以及11例患者队列中2个CYLD突变的功能影响：我们的研究结果表明，HPV阳性HNSCC中CYLD的改变与转移和不良预后有关。

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CYLD Alterations Are Associated With Metastasis and Poor Prognosis in Human Papilloma Virus-Positive Head and Neck Cancer.

Background: Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an emerging epidemic and a subset of HPV-positive patients experience aggressive disease with metastases. The CYLD gene is frequently altered in HPV-positive HNSCC, but the role of these alterations in disease progression is poorly understood.

Methods: We identified 11 HPV-positive HNSCC patients with CYLD alterations and assessed their clinical course. We also characterized a unique, HPV-positive, metastatic, HNSCC patient-derived xenograft (PDX).

Results: All 11 patients developed metastasis with reduced overall survival when compared with metastatic HPV-positive patients with wild-type CYLD. The metastatic PDX harbored a CYLD mutation (S371*) and exhibited reduced expression of connexin 43, a potentially antimetastatic protein. We also investigated the functional impact of the S371* mutation, as well as 2 CYLD mutations from our 11-patient cohort.

Conclusion: Our findings indicate that alterations in CYLD in HPV-positive HNSCC are associated with metastasis and poor prognosis.

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来源期刊

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 医学-耳鼻喉科学

CiteScore

7.00

自引率

6.90%

发文量

278

审稿时长

1.6 months

期刊介绍： Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.